EMA keeps Oxbryta off the EU market after review finds more deaths

On 17 October the European Medicines Agency announced that its human medicines committee had concluded a review begun in July 2024 and recommended that the marketing authorisation for Oxbryta remain suspended [s1]. The committee found that the benefits of the medicine no longer outweigh its risks [s1].

Oxbryta contains voxelotor and was authorised in February 2022 to treat haemolytic anaemia in patients aged 12 and over with sickle cell disease, alone or with hydroxycarbamide [s1]. It has not been available in the EU since September 2024, when CHMP suspended it as a precautionary measure [s1]. The October decision converts a temporary hold into a settled conclusion.

What the review found

The review examined data from two clinical trials [s1].

In the first, which assessed voxelotor in people with sickle cell disease at higher risk of stroke, eight children treated with Oxbryta died compared with two children who received placebo [s1].

In the second, which evaluated the medicine for leg ulcers — a known complication of sickle cell disease — one person died in the Oxbryta group during the first 12 weeks, with no deaths in the placebo group [s1]. In the following 12-week phase, in which all patients received Oxbryta, eight further deaths were reported [s1].

Both studies also showed more sudden episodes of severe pain, including vaso-occlusive crises, among patients treated with Oxbryta than among those on placebo [s1].

The signal that started this was not the signal that ended it

The sequence matters, because it is an unusually clear illustration of how a safety review can change shape while it runs.

CHMP recommended suspension on 26 September 2024 as a precautionary measure after data from two registry-based studies indicated that patients were experiencing a higher frequency of sudden pain episodes on Oxbryta than before starting treatment [s1]. At that point EMA advised healthcare professionals that Oxbryta should no longer be prescribed and that existing patients should be switched to an alternative treatment [s1].

The final analysis of those registry studies did not confirm an increase in sudden pain episodes [s1]. Had that been the only evidence, the suspension might have been lifted. But by then the clinical trial data had arrived, and the trials showed both more pain episodes and more deaths [s1].

EMA notes that these results are inconsistent with the earlier main clinical trial that supported the original authorisation, which had shown no difference between treatment groups [s1].

What the original trial had shown

That earlier trial, published in 2019, randomised 274 participants 1:1:1 to voxelotor 1500 mg, voxelotor 900 mg, or placebo once daily [s3]. Its primary endpoint was haemoglobin response — an increase of more than 1.0 g/dL from baseline at week 24 — and 51 percent of the 1500 mg group met it against 7 percent on placebo [s3]. The 1500 mg group also had significantly greater reductions in indirect bilirubin and reticulocyte percentage [s3]. The percentage of participants with an adverse event that occurred or worsened during treatment was similar across groups [s3].

That is a textbook surrogate-endpoint approval: the drug reliably raised haemoglobin, which is the biochemical consequence of inhibiting sickle haemoglobin polymerisation, and the safety profile looked unremarkable in 274 people over 24 weeks. What it did not establish is whether raising haemoglobin by that mechanism improves how patients actually do.

Why the committee could not narrow the suspension

CHMP stated that the underlying mechanisms for the increased deaths and complications remain unclear [s1]. It found no clear explanation for the increased risks, and — the operative finding — could not identify measures that would effectively minimise them, nor any subgroup of patients for whom the benefits would outweigh the risks [s1].

Regulators routinely respond to a safety signal by narrowing an indication, adding warnings, or restricting use to a defined population. That option requires knowing who is at risk and why. Without a mechanism and without an identifiable safer subgroup, there is nothing to narrow to.

In reaching its opinion the committee took advice from experts in the field and from patient representatives, and consulted EMA's safety committee, PRAC, on potential risk minimisation measures [s1].

The procedure, and what remains

The review was initiated on 29 July 2024 at the request of the European Commission under Article 20 of Regulation (EC) No 726/2004 [s1]. The CHMP opinion goes to the Commission, which will issue a final legally binding decision applicable in all EU member states [s1]. The October CHMP meeting highlights record the outcome as a public-health recommendation alongside the meeting's other business [s2].

Until that decision, and in practice since September 2024, Oxbryta remains unavailable for prescription in the EU [s1].

What this leaves

Sickle cell disease is a genetic condition in which an abnormal form of haemoglobin makes red blood cells rigid and sticky and changes their shape from disc to crescent [s1]. Patients whose treatment was switched a year ago have already made whatever adjustment they were going to make; for them this announcement is a confirmation rather than a change.

What is genuinely unresolved is the mechanism. A drug that raises haemoglobin was associated with more vaso-occlusive crises and more deaths in two trials, and nobody yet has a published explanation for how that happens. Until someone does, the finding constrains not just voxelotor but the assumption that haemoglobin response is a dependable stand-in for benefit in sickle cell disease.

Sources

• EMA confirms suspension of sickle cell disease medicine Oxbryta — European Medicines Agency, 17 October 2025
• Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 13-16 October 2025 — European Medicines Agency, 17 October 2025
• A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease — The New England Journal of Medicine, 14 June 2019